Expression of Gemcitabine-resistance-related gene and polymorphism of ribonucleotide reductase M1 gene promoter in Gemcitabine-resistant A549/Gem and NCI-H460/Gem cell lines.
- Author:
Xiao-qing LIU
1
;
Wei-xia WANG
;
Li LIN
;
San-tai SONG
Author Information
- Publication Type:Journal Article
- MeSH: Antimetabolites, Antineoplastic; pharmacology; Carcinoma, Large Cell; genetics; metabolism; pathology; Carcinoma, Non-Small-Cell Lung; genetics; metabolism; pathology; Cell Line, Tumor; Cytidine Deaminase; genetics; metabolism; DNA-Binding Proteins; genetics; metabolism; Deoxycytidine; analogs & derivatives; pharmacology; Deoxycytidine Kinase; genetics; metabolism; Drug Resistance, Neoplasm; Endonucleases; genetics; metabolism; Humans; Lung Neoplasms; genetics; metabolism; pathology; PTEN Phosphohydrolase; genetics; metabolism; Polymorphism, Single Nucleotide; Promoter Regions, Genetic; RNA, Messenger; metabolism; Tumor Suppressor Proteins; genetics; metabolism
- From: Chinese Journal of Oncology 2010;32(1):17-21
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVETo assay the expression of cytidine deaminase (CDA), ribonucleotide reductase subunit 1 (RRM1), phosphatase and tensin homologue deleted from chromosome 10 (PTEN), excision repair cross-complementation group 1 (ERCC1), deoxycytidine kinase (dCK) and RRM1(-)37A/C polymorphism, which have been shown relevant to gemcitabine resistance in two human gemcitabine-resistant non-small cell lung cancer cell lines A549/Gem and NCI-H460/Gem, so as to make clear how do they vary during the course of acquiring resistance to gemcitabine.
METHODSThe human gemcitabine-resistant non-small cell lung cancer cell lines A549/Gem and NCI-H460/Gem were established in our Department by repeated clinical serum peak concentration and gradually increasing doses. Real-time fluorescent quantitative PCR was used to examine the expression of CDA, RRM1, PTEN, ERCC1, dCK and RRM1(-)37A/C polymorphism in those cell lines at different time points during their induction process.
RESULTSThe resistance indexes of A549/Gem and NCI-H460/Gem cells reached 163.228 and 181.684, and then remained stable at 115.297 and 129.783, respectively. The expression of CDA, RRM1, PTEN and ERCC1 varied along with the changing gemcitabine resistance indexes, but expression of dCK did not change apparently. The wild type promoter was able to amplify the genomic DNA in different induction stages of A549/Gem and NCI-H460/Gem cells, but allelotype did not, indicating that the gene type of A549/Gem, NCI-H460/Gem and their parental cells remaining still wild type.
CONCLUSIONCompared with their parental cells, the expressions of CDA, RRM1, PTEN and ERCC1 in human gemcitabine-resistant non-small cell lung cancer cell lines A549/Gem and NCI-H460/Gem rise, the expression of dCK changes inapparently, therefore, their gene type are remaining wild type.
